Study Rundown:Early in the progression of lung cancer symptoms are rare, but persistent cough, dyspnea, chest pain, and/or weight loss may be experienced in advanced forms of the disease. Most lung cancers are caused by exposure to tobacco smoke. Because symptoms are rare in early forms of the disease it is recommended for people at increased risk for lung cancer to undergo regular screenings. Results from the National Lung Screening Trial (NLST) indicated chest CT screenings can decrease lung cancer deaths significantly relative to screenings with chest x-rays. In addition, the NLST study indicated CT screening leads to more false positives than chest x-rays, with the false positive rate hovering at approximately 98%.

The NLST defined a positive lung CT screening result to be a nodule greater than 4 mm in diameter with no benign calcification patterns. Because increasing the threshold to diagnose a lesion as cancerous can theoretically decrease the false positive rate but also decrease the sensitivity of the screening procedure, questions have been raised about changing the thresholds for positive cancer diagnosis. Additionally, management of patients with positive screening results has not been truly standardized. Lung-RADS has sought to address these issues by increasing the thresholds for a positive screening test and providing management guidelines on how to proceed after screening. Retrospective studies by McKee and colleagues and Pinsky and colleagues indicate the PPV of CT screenings of high-risk patients can be raised significantly with small or no decreases in sensitivity.

In-Depth [retrospective cohorts]: Pinsky and colleagues applied the Lung-RADS criteria to published data from the NLST. Patients aged 55-74 who smoked for 30+ pack-years and still smoked or had quit in the last 15 years were recruited at 33 US institutions for the study (n=26 455). Patient and nodule level information was available for analysis. To assess Lung-RADS, nodules were reclassified using categories ranging from 1 (negative screening) to 4 (suspicious), with Category 4 having various subcategories. Classification of nodules using Lung-RADS accounts for nodule size, attenuation, and nodule growth in follow-up screenings. Positive results, as well as follow-up and management guidelines, are detailed in Table I. The patient’s screening category is based off the nodule with the highest Lung-RADS score. Lung cancer was considered present at a given screening if the diagnosis was made within 1 year of screening or before the next screening. When applying Lung-RADS criteria to baseline and follow-up screenings false-positive rates and sensitivity were significantly lower.

McKee and colleagues also retrospectively assessed application of Lung-RADS criteria to CT lung cancer screenings originally assessed using National Comprehensive Cancer Network (NCCN) criteria. Patients were assessed at a single center and had to be at high-risk for lung cancer (as defined by NCCN), asymptomatic, have physician orders for CT lung screening, been cancer free the previous 5+ years, and not have metastatic disease (n=2180). Reclassification of nodules to benign using Lung-RADS occurred in 17% (370/2180) of patients, decreasing positive test rates from 27.6% using NCCN criteria to 10.6%. No patients diagnosed with lung cancer following screening had their nodules reclassified to benign. The PPV of baseline CT screening increased from 6.9% to 17.3%. Of 29 patients diagnosed with lung cancer on follow-up, 86.3% (25/29) were classified as Category 4.

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